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X-linked non-syndromic intellectual disability

Synonym(s) X-linked non-specific intellectual disability
Prevalence Unknown
Inheritance X-linked recessive
Age of onset Childhood
ICD-10 -
MeSH -
MedDRA -


Disease definition

Nonspecific X-linked intellectual deficiencies (MRX) belong to the family of sex-linked intellectual deficiencies (XLMR). In contrast to syndromic or specific X-linked intellectual deficiencies (MRXS), which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only symptom of MRX.


The incidence of MRX among males is about 1/900 and these conditions represent two thirds of the familial cases of X-linked intellectual deficiency.

Clinical description

However, the natural history, severity and clinical aspect of MRX often vary from one sibling to another in a given family. In addition, a history of minor physical signs (such as mild neonatal hypotonia, hyperreflexia, mild microcephaly, slightly small stature, a few convulsive seizures or secondary arrest of acquisition of verbal skills) may be reported and although they are generally considered as banal they are characteristic for a given family.


Seventeen different genes responsible for MRX have been identified to date. Most of the corresponding proteins are involved, either directly or through a regulatory function, in the growth of nerve cells or in synaptic communication between these cells. These proteins play a role in learning and/or memory. Encephalic function and/or development or neuronal plasticity is impaired in MRX patients. In addition, specific mutations in MRXS genes have been discovered in some MRX families. Finally, additional genes clearly remain to be uncovered as the causative gene has not yet been identified in half the MRX families. However, the identification of the genes involved in many families now makes it possible to perform a clinical study using a gene by gene approach. A fine approach using neurological, psychological and psychiatric tools and high quality medical imaging has allowed certain features, such as an evocative morphological anomaly of the cerebellar vermix (OPHN1 gene) or very specific motor disorders of the hands (ARX gene), to be substantiated. Thus, some forms that were previously classified as `non specific' (MRX) have been progressively shown to have a gene-dependant specificity (MRXS). It might be possible, in the future, to identify a specific phenotype for each MRX gene, which might allow an efficient and economic examination protocol to be designed for male patients suffering from intellectual deficiency. The finding of several signs will orientate the diagnosis towards one form or another of MRX, and hence the linkage to X chromosome may be identified even if only a single boy is affected.

Diagnostic methods

As intellectual deficiency is the key symptom and no specific physical signs are observed during routine examinations, to date the diagnosis of MRX is only considered in cases of typical X-linked familial recurrence. Extensive investigations should be carried to search for a potential recurrence in the families of all male patients presenting with isolated, permanent intellectual deficit for which no cause has been found.

Genetic counseling

Genetic counselling is the only preventive measure available.

Management and treatment

There is currently no specific treatment.

Expert reviewer(s)

  • Dr Claude MORAINE

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